CBNS 101 lecture9

CBNS 101 lecture9 - Signal sequences on proteins act as...

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n Signal sequences direct proteins to correct cellular address. n Recognized by specialized receptor proteins that mediate transport. In some cases, the localization of the receptor is restricted in the cell. Signal sequences on proteins act as "address tags z
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All of these processes require energy. 1. Gated transport through nuclear pores. Transport occurs post-translationally; folded protein moves through nuclear l gate z 2.Transmembrane transport. a) Post-translational insertion of unfolded protein through lipid bilayer of mitochondria, chloroplasts, peroxisomes. b) Co-translational insertion of protein into ER. 3. Vesicular transport. After insertion into ER, proteins further transported by vesicles into Golgi, lysosomes, cell surface. Three ways in which address tags are used to direct protein transport.
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Nuclear Pore Complexes or nucleoporins: Gateway for Transport In and Out of the Nucleus n Huge complex, 100-nm wide circular openings in the nuclear envelope. n Can open to 25 nm in diameter. ~3000-4000 NPCs in typical mammalian cell. n Transport is not limited to proteins - includes ribonucleoproteins (RNPs). n Transport across the NPC is bidirectional . n Proteins do not need to be unfolded to pass through pore. n Passage through the NPC does not allow proteins to integrate into adjacent bilayer. n Assembled from ~30 (yeast) to over 50 (vertebrates) proteins called nucleoporins (nups).
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General mechanism of transport through nuclear pores Nuclear localization signal (NLS) proteins interact with a class of proteins that speciFcally bind to the NLS region in the cytoplasm: The nuclear import receptor The nuclear import receptor is localized to the pore by virtue of its ability to interact with ±G repeats on proteins that comprise the Fbrils of the nuclear pore. These interactions help transport the receptor:cargo protein complex through the pore. Once through the pore receptor dissociates from the cargo protein.
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The Ran GTPase Drives Directional Transport through Nuclear Pores Complexes Receptor only binds to Ran-GTP, not Ran-GDP. In the nucleus, import receptors are thought to release their cargo because a high concentration of Ran-GTP competes for Nuclear Localization Signal binding
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A nuclear/cytoplasmic gradient of Ran-GDP/Ran-GTP provide the free energy for active nuclear transport Gradient is maintained by asymmetric distribution of proteins that influences Ran GTP hydrolysis. One protein is called Ran-GEF(Guanine nucleotide exchange factor), ensures rapid exchange of Ran-GDP for Ran-GTP. The Ran- GEF has a NLS and interacts with DNA in nucleus Ran GTP hydrolysis is greatly stimulated by another protein called Ran-GAP (GTPase- activating protein), localized in cytoplasm. CYTOSOL
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This note was uploaded on 05/26/2011 for the course CBNS 101 taught by Professor - during the Spring '08 term at UC Riverside.

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CBNS 101 lecture9 - Signal sequences on proteins act as...

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